Educational results of the Japan Maternal Emergency Life-Saving (J-MELS) simulation training organized by Japan Council for the Implementation of the Maternal Emergency Life-Saving System (J-CIMELS): a 12-month longitudinal follow-up study in Japan.

AIMS: This study aimed to evaluate the long-term results of Japan Maternal Emergency Life-Saving (J-MELS) simulation training on obstetric healthcare providers, over a 12-month follow-up period. METHODS: A total of 273 trainees from 17 J-MELS Basic courses conducted between August 2021 and October 2023 were included. The trainees' responses to the pre- and post-tests, questionnaires, and self-reports on the usefulness of the J-MELS scenarios in actual clinical settings at 1, 6, and 12 months after the training were analyzed. Multivariate logistic regression analysis was also conducted to identify the factors influencing knowledge retention. RESULTS: We found an overall improvement in clinical knowledge acquisition after J-MELS training and a significant retention of this improvement at least until 12 months later. However, these scores gradually declined over. Trainees reported increased usefulness of J-MELS scenarios in actual clinical practice at 1, 6, and 12 months after training, particularly in managing obstetric emergencies such as atonic postpartum hemorrhage. Knowledge retention was influenced by several specific factors, such as years of clinical experience, affiliated institutions, qualifications, and especially pre-test scores. CONCLUSION: Our longitudinal follow-up study demonstrated, for the first time, the long-term results of J-MELS simulation training using post-tests and self-report data. Our findings provide valuable insight into the impact of J-MELS simulation training on maternal emergency care. By elucidating the factors influencing knowledge retention and practical utility, the findings offer actionable recommendations for optimizing training strategies and improving maternal outcomes in actual clinical practice.

Impact of a multi-professional expert team on EOL care of children with cancer.

BACKGROUND: The quality of end-of-life (Q-EOL) care is influenced by various factors such as resources for palliative care (PC). We introduced a multi-professional expert team (MET) in 2014, which provides home-based care for children and adolescents with incurable cancer. This study investigated the impacts of the outreach activities by the MET on Q-EOL care of pediatric oncology patients. METHODS: This observational study retrospectively examined 112 patients receiving end-of-life care between 1989 and 2018 at a pediatric cancer center in Japan. Some of the indicators of Q-EOL care before and after the introduction of the outreach activities by the MET were compared. The subjects were 92 in pre-MET and 20 in post-MET periods. RESULTS: The median number of days for which the patients stayed at home during the final seven or 30 days were significantly prolonged in the post-MET period (0.0 vs 1.5 days, P = 0.020, 3.0 vs 12.0 days, P = 0.042). The change was more significant in hematologic malignancies than solid and central nervous system tumors. Patients receiving longer PC before their deaths could stay at home longer during the last 7 days. The ratio of patients receiving PC for more than 2 months was significantly increased in post-MET period (60.9 vs 90.0%, P = 0.014). More patients also greeted their deaths at home in the post-MET period (3.3 vs 25.0%, P < 0.001). CONCLUSIONS: The activities of the MET transformed the end-of-life care of children and adolescents with incurable cancer. Earlier transitions to PC from curative treatment were associated with longer home-based care and more deaths at home.

Interaction between a plasma membrane-localized ankyrin-repeat protein ITN1 and a nuclear protein RTV1.

The increased tolerance to NaCl 1 (ITN1) protein is a plasma membrane (PM)-localized protein involved in responses to NaCl stress in Arabidopsis. The predicted structure of ITN1 is composed of multiple transmembrane regions and an ankyrin-repeat domain that is known to mediate protein-protein interactions. To elucidate the molecular functions of ITN1, we searched for interacting partners using a yeast two-hybrid assay, and a nuclear-localized DNA-binding protein, RTV1, was identified as a candidate. Bimolecular fluorescence complementation analysis revealed that RTV1 interacted with ITN1 at the PM and nuclei in vivo. RTV1 tagged with red fluorescent protein localized to nuclei and ITN1 tagged with green fluorescent protein localized to PM; however, both proteins localized to both nuclei and the PM when co-expressed. These findings suggest that RTV1 and ITN1 regulate the subcellular localization of each other.

Acute motor-sensory axonal Guillain-Barré syndrome with unilateral facial nerve paralysis after rotavirus gastroenteritis in a 2-year-old boy.

Guillain-Barré syndrome (GBS) is well known as presenting with acute immune-mediated polyneuropathies, with strong associations with antecedent infections. Several variant forms of GBS have been described, including acute inflammatory demyelinating polyneuropathy, acute motor axonal neuropathy, acute motor-sensory axonal neuropathy, and sensory GBS. We present a rare case of 2-year-old boy with acute motor and sensory polyneuropathy and left-sided facial nerve paralysis after rotavirus infection. He received immunoglobulin i.v. with subsequent satisfactory recovery.

An alternative approach to the monitoring of respiration by dynamic air-pressure sensor.

Monitoring and assessing of patient respiratory function during conscious sedation are important because many drugs used for conscious sedation produce respiratory depression and subsequent hypoventilation. The purpose of this study is to assess the value of a dynamic air-pressure sensor for respiratory monitoring of clothed patients. Eight clothed adult volunteers were reclined on a dental chair positioned horizontally. The air bag for measuring air-pressure signals corresponding to respiration was placed on the seat back of the dental chair in the central lumbar area of the subject. The subject breathed through a face mask with a respirometer attached for measuring expiratory tidal volume. The air-pressure signals corresponding to respiration were obtained and the time integration values for air pressure during each expiration (integral P(exp)) were calculated. The expiratory tidal volume (TV(exp)) was measured simultaneously by respirometer. The relationship between TV(exp) and integral P(exp) for each subject was assessed by a Pearson correlation coefficient. A strong correlation between TV(exp) and integral P(exp) was observed in all subjects. Measuring integral P(exp) by dynamic air-pressure sensor makes it possible to estimate respiratory volume breath by breath, and the respiratory pressure-time integral waveform was useful in visually monitoring the respiration pattern. We believe that in the future this device will be used to monitor respiratory physiology in clothed patients, contributing to safer sedative procedures.

Suppression of beta-catenin mutation by dietary exposure of auraptene, a citrus antioxidant, in N,N-diethylnitrosamine-induced hepatocellular carcinomas in rats.

Alteration of beta-catenin expression in hepatocellular carcinomas (HCCs) may play an important role in tumor progression by stimulating cell proliferation. We have previously reported that auraptene (AUR), an antioxidant agent isolated from citrus fruit, effectively inhibits chemically induced hepatocarcinogenesis in rats. In this study, we investigated the molecular mechanism of the inhibitory effects of dietary supplementation with AUR on N,N-diethylnitrosamine (DEN)-initiated hepatocarcinogenesis. Male F344 rats initiated with DEN were fed the AUR-containing diet during either the initiation stage (initiation feeding for 7 weeks) or post-initiation phase (post-initiation feeding for 25 weeks) of hepatocarcinogenesis. Liver tumors >5 mm in diameter were used for the analysis of beta-catenin gene mutation and beta-catenin protein expression. After PCR amplification of exon 2 of the beta-catenin gene, the products were sequenced directly. Mutations in the beta-catenin gene were detected in 8 of 24 HCCs (33.3%) in the DEN alone group, 7 of 15 HCCs (46.7%) in the DEN + AUR (initiation feeding) group, and 0 of 8 HCCs (0%) in the DENright curved arrow AUR (post-initiation feeding) group. No mutations of beta-catenin gene were detected in liver cell adenomas of any group. These results demonstrate that AUR exposure in post-initiation period suppresses the occurrence of HCCs with beta-catenin mutation, presumably by negative selection for neoplastic cells harboring the mutation.

Papillary endothelial hyperplasia and dilated lymphatic vessels in bullous pilomatricoma.

This is a report of papillary endothelial hyperplasia in a 9-year-old girl with a pilomatricoma showing bullous appearance. Histologically, papillary proliferation of endothelial cells was found within dilated lymphatic endothelium-lined vascular channels overlying a pilomatricoma. The endothelial cells covering the papillae were of a lymphatic endothelial cell nature proved by immunohistochemistry and electron microscopy. Abundant fibrous long-spacing collagen was observed in the connective tissue and fibroblasts within papillae.

Dietary supplementation of the citrus antioxidant auraptene inhibits N,N-diethylnitrosamine-induced rat hepatocarcinogenesis.

OBJECTIVES: We have previously reported that an antioxidant, auraptene (AUR), isolated from citrus fruit effectively inhibits chemically induced carcinogenesis in digestive tracts, such as the oral cavity, esophagus and large bowel. In this study, we investigated the modifying effects of dietary supplementation with AUR on N,N-diethylnitrosamine (DEN)-initiated hepatocarcinogenesis in male F344 rats in two different experiments to determine whether the compound exerts a cancer-chemopreventive action in other organs. METHODS: In the first experiment, animals were fed diets containing AUR at dose levels of 100 and 500 ppm for 7 weeks 1 week before, during, and 1 week after the start of liver carcinogenesis induced by DEN (40 ppm in drinking water for 5 weeks) to predict the modulatory effect on hepatocarcinogenesis. After 7 weeks, the numbers of hepatocellular enzyme-altered foci (EAF; cm(2)) which stained positive for the placental form of glutathione S-transferase (GST-P) and transforming growth factor (TGF)-alpha were determined on immunohistochemically stained sections. In the second experiment conducted to confirm the findings, animals subjected to DEN treatment were fed AUR-containing diets (100 and 500 ppm) during either the initiation stage ('initiation' feeding for 7 weeks) or post-initiation phase ('post-initiation' feeding for 25 weeks) of DEN-induced hepatocarcinogenesis. RESULTS: In the first experiment, feeding with AUR at both doses during DEN exposure decreased the mean numbers of GST-P-positive and TGF-alpha-positive EAF/cm(2), and the reduction in the number of TGF-alpha-positive EAF by feeding 500 ppm AUR was statistically significant (p < 0.005). In the second experiment, the 'initiation' feeding with 500 ppm AUR significantly inhibited the incidence (33 vs. 83%, p = 0.000511) and multiplicity (0.67 +/- 1.09 vs. 1.96 +/- 1.85, p < 0.005) of liver cell carcinoma. Also, the 'post-initiation' feeding with AUR at both doses significantly reduced the development of hepatocellular carcinoma (100 ppm: incidence, 15%, p = 0.000006; multiplicity: 0.25 +/- 0.64, p < 0.001; 500 ppm: incidence, 11%, p = 0.000002; multiplicity, 0.26 +/- 0.81, p < 0.001). In addition, AUR feeding reduced cell proliferation and the apoptotic index in liver cell neoplasms. CONCLUSIONS: The results suggest that the citrus antioxidant AUR is a potential chemopreventive agent against DEN-induced hepatocarcinogenesis in rats.

Enhancement of development of azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice.

Epidemiological studies have shown that obesity and diabetes mellitus may be risk factors for colon cancer. However, the underlying mechanisms of how these chronic diseases promote colon carcinogenesis remain unknown. C57BL/KsJ-db/db mice have obese and diabetic phenotypes because of disruption of the leptin receptor. The present study was designed to investigate whether development of azoxymethane (AOM)-induced dysplastic and early neoplastic (premalignant) lesions of the colon is modulated in db/db mice. Homozygous db/db mice, heterozygous db/+ mice and littermate controls (+/+) were injected with AOM under food restriction ( approximately 10.8 kcal/mouse/day) and killed 5 weeks after the carcinogen treatment. Their colons were assessed for premalignant lesions induced by AOM. We found a significant increase in the multiplicity of the total premalignant lesions in db/db mice when compared with db/+ or +/+ mice. Phenotypically, serum leptin and insulin levels in db/db mice were significantly higher than those in db/+ or +/+ mice, whereas the body weights and glucose levels in blood of db/db, db/+ and +/+ mice were comparable. In addition, immunostaining of the leptin receptor and insulin-like growth factor-I receptor showed up-regulation of these protein levels specifically in the lesions. Our data indicate that development of AOM-induced premalignant lesions is enhanced in db/db mice with hyperleptinemia and hyperinsulinemia. The results have important implications for further exploration of the possible underlying events that affect the positive association between colon cancer and chronic diseases (obesity and diabetes).

Inhibition of inducible isoforms of cyclooxygenase and nitric oxide synthase by flavonoid hesperidin in mouse macrophage cell line.

Previous data have shown that a citrus flavanone, hesperidin possesses chemopreventive efficacies. We designed to investigate the inhibitory effect of hesperidin on lipopolysaccharide (LPS)-induced over-expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) proteins, over-production of prostaglandin E2 (PGE2) and nitric oxide (NO) using mouse macrophage cells. Treatment with hesperidin suppressed production of PGE2, nitrogen dioxide (NO2), and expression of iNOS protein. In the case of COX-2, hesperidin did not affect the protein level. Our data indicate hesperidin as a COX-2 and iNOS inhibitor, which might be related to the anti-inflammatory and anti-tumorigenic efficacies.

Preventive effect of fermented brown rice and rice bran on diethylnitrosoamine and phenobarbital-induced hepatocarcinogenesis in male F344 rats.

Epidemiological and preclinical studies have suggested that nutrition plays an important role in the etiology of cancer. Our group previously demonstrated that rice germ or fermented brown rice has a preventive effect on colorectal carcinogenesis. The experiment described here was examined for the potential anticancer properties of brown rice fermented by Aspergillus Oryzae (FBRA) in male F344 rats using inhibition of diethylnitrosoamine (DEN) and phenobarbital (PB)-induced hepatocarcinogenesis as the measure of preventive efficacy when this agent was administered at 5% and 10% levels in diet during initiation phase (during and until 1 week after carcinogen treatment) or post-initiation phase (beginning 1 week after carcinogen treatment) of the carcinogenesis. Rats were sacrificed 20 weeks after the initiation of DEN treatment (200 mg/kg body weight, once weekly for 3 weeks). Expression of liver tumors was evaluated histopathologically. Administration of 10% FBRA in the diet during the initiation phase significantly decreased the incidence (43% vs. 8%) and multiplicity (0.5+/-0.6 vs. 0.1+/-0.3) of hepatocellular carcinoma (HCC) as compared to those given the control diet. In addition, 5% and 10% of FBRA in the diet during post-initiation phase significantly decreased the incidence of HCC (43% vs. 15% and 9%, respectively) and multiplicity of hepatocellular adenoma (4.7+/-3.7 vs. 2.1+/-2.2 and 2.4+/-1.4, respectively) and HCC (0.5+/-0.6 vs. 0.2+/-0.4 and 0.1+/-0.3, respectively). These data prove that FBRA has an inhibitory effect on the hepatocarcinogenesis in rats. FBRA could be a promising chemopreventive agent for human liver as well as colorectal neoplasia.

Inhibitory effects of troglitazone, a peroxisome proliferator-activated receptor gamma ligand, in rat tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide.

Ligands for peroxisome proliferator-activated receptor (PPAR) gamma have been implicated in growth inhibition and cell differentiation in certain malignancies. In this study, the effects of troglitazone, a PPAR gamma ligand, given during the postinitiation phase of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. Rats aged 6 weeks were given 4-NQO at 20 ppm for 8 weeks to induce tongue neoplasms. Starting 1 week after the cessation of 4-NQO exposure, animals were fed diets containing 0, 30 or 100 ppm troglitazone for 22 weeks. At the end of the study (week 32), the incidences of 4-NQO-induced tongue neoplasms and preneoplasms were determined histopathologically and cell proliferation activity was estimated by counting bromodeoxyuridine (BrdU)-labeling indices and cyclin D1-positive cell ratios. In addition, immunohistochemical expression of cyclooxygenase (COX)-2 and PPAR gamma was assessed in the tongue lesions. Feeding with 100 ppm troglitazone significantly decreased the incidence of squamous cell carcinoma when compared to the group without troglitazone treatment (5.0% vs. 45.8%, P < 0.005). Interestingly, the BrdU-labeling index and cyclin D1-positive cell ratio assessed in the non-lesional tongue squamous epithelium were reduced by dietary administration of troglitazone (P < 0.0001-0.005). Additionally, the immunoreactivity of COX-2 in the tongue lesions was also decreased by the treatment (P < 0.01-0.05). These results clearly showed that dietary troglitazone inhibits 4-NQO-induced tongue carcinogenesis and such inhibition is related to suppression of increased cell proliferation and/or COX-2 expression. This study warrants further investigation on the use of PPAR gamma ligands as a novel preventive approach for oral malignancy.

Promoting effects of high-fat corn oil and high-fat mixed lipid diets on 7,12-dimethylbenz[a]anthracene-induced mammary tumorigenesis in F344 rats.

Epidemiological studies and laboratory animal model assays suggest that a high intake of dietary fat promotes mammary carcinogenesis as well as colon tumorigenesis. Fat intake in the United States traditionally includes high amounts (30% of total caloric intake) of saturated fatty acids (SFAs) compared to polyunsaturated fatty acids (PUFAs). A recent study suggested that a high-fat mixed-lipid diet (HFML), which simulates the mixed-lipid and high SFAs composition of the average American diet, strongly promotes rat colon carcinogenesis, even when compared to another high-fat diet containing PUFA-rich corn oil. On the other hand, some reports suggest that a high-fat diet rich in n-6 PUFAs promotes mammary carcinogenesis more strongly than a high-fat diet rich in SFAs. Therefore, the present study was designed to compare the effects of HFML, high-fat corn oil diet (HFCO) that is rich in n-6 PUFAs, and a low-fat corn oil diet (LFCO) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female F344 rats. At 7 weeks of age, female F344 rats intended for carcinogen treatment received a gavage of DMBA at a dose level of 65 mg/kg of body weight. Beginning 1 week after carcinogen treatment, groups of rats were then maintained on experimental diets containing LFCO, HFCO or HFML. All rats were evaluated weekly by palpation of mammary tumors and sacrificed 20 weeks after the DMBA treatment. Palpable tumors of mammary glands were detected at the 8, 11, and 19 weeks in the HFCO, HFML and LFCO groups, respectively. Histopathological observation revealed that the incidence and number of mammary tumors in the HFCO group were significantly higher than in the LFCO group. Rats on the HFML diet tended towards a higher incidence and number of mammary tumors compared with the LFCO group, although the correlation was not statistically significant. These results suggest that, for this animal model, both the HFCO and HFML diets promote DMBA-induced mammary carcinogenesis when compared to the LFCO diet, and that the HFCO diet is more tumor-promotional than the HFML diet.

Decisive role of electronic polarization of the protein environment in determining the absorption maximum of halorhodopsin.

It is known that the absorption maximum of halorhodopsin is red shifted by 10 nm with the uptake of a chloride ion Cl(-). According to the X-ray structure, the ion is located at the position of the counterion of the chromophore, protonated retinal Schiff base. Thus, the direction of the observed spectral change is opposite to that expected from the pi-electron redistribution (an increase in the bond alternation) induced by the counterion. The physical origin of this abnormal shift is never explained in terms of any simple chemical analogues. We successfully explain this phenomenon by a QM/MM type of excitation energy calculation. The three-dimensional structure of the protein is explicitly taken into account using the X-ray structure. We reveal that the electronic polarization of the protein environment plays an essential role in tuning the absorption maximum of halorhodopsin.

Carcinoid tumor in the female urethral orifice: rare case report and a review of the literature.

We experienced an extremely rare tumor in the female urethral orifice in a 57-year-old Japanese woman. To our knowledge, only two cases of primary urethral carcinoid tumor have been reported. The previous reports of urethral carcinoid tumor were recognized in the male middle urethra and penile urethra. The present case was resected, and diagnosed as a carcinoid tumor by histological, immunohistochemical and ultrastructural findings. The tumor cells were stained by chromogranin A, synaptophsin and neuron-specific enolase, and neurosecretory granules were confirmed with electron microscopy. The patient did not complain of any symptoms until 5 years after the resection of the tumor. Therefore, the case we describe here is the first known report of carcinoid tumor in the Japanese female urethra.

Azoxymethane-induced beta-catenin-accumulated crypts in colonic mucosa of rodents as an intermediate biomarker for colon carcinogenesis.

It is now well established that bile acids act as colon tumor promoters. However, a previous study provided conflicting data showing that dietary exposure of cholic acid (CHA), a primary bile acid, inhibits the carcinogen-induced formation of aberrant crypt foci (ACF), possible preneoplastic lesions, in colonic mucosa of rodents. Recently we found beta-catenin-accumulated crypts (BCAC) in colonic mucosa of rats initiated with azoxymethane (AOM) and provided evidence that BCAC might be preneoplastic lesions independent from ACF. In the present study, we investigated the modifying effects of dietary CHA on the formation of BCAC as well as ACF in male F344 rats after exposure to AOM to determine if the differences in the effect of CHA on these lesions could account for this discrepancy. The results indicate that administration of CHA (0.5%) in the diet during the post-initiation phase significantly reduced the total number, multiplicity and size of ACF (P < 0.00001) in AOM-exposed colonic mucosa as reported previously. The number of ACF even with >4 aberrant crypts/focus was also decreased significantly (P < 0.0002), suggesting that the large ACF are little resistant to continuous feeding of 0.5% CHA diet. Interestingly, the dietary CHA significantly enhanced both the multiplicity (P < 0.002) and size (P < 0.00001), but not the incidence, of AOM-induced BCAC when compared with the control diet group. Importantly, the number of large BCAC with >6 crypts/lesion was increased significantly by the dietary CHA (P < 0.003). Our results support the concept that BCAC are precursors of colon tumors and indicate the usefulness of BCAC as intermediate biomarkers for colon carcinogenesis, although the methodology for their detection requires further improvement.

Further investigation of the modifying effect of various chemopreventive agents on apoptosis and cell proliferation in human colon cancer cells.

PURPOSE: Recent preclinical assays using animal models have shown that naturally-occurring and synthetic chemicals such as auraptene (AUR), nobiletin (NOB), hesperidin (HE), diosmin (DIO), indole-3-carbinol (I3C), 1'-acetoxychavicol acetate (ACA), 2,5-di-O-acetyl-D-1,4-glucaro-6,3-dilactone (ACE), D-glucuronic acid gamma-lactone (GL), chlorogenic acid (CGA), protocatechuic acid (PA), and sinigrin (SIN) are possible preventive agents against the development of cancer. However, the mode of action of such preventive agents remains to be elucidated. The current study, therefore, was conducted to analyze whether these agents induce apoptosis and/or inhibit DNA synthesis in human colorectal cancer cell lines. METHODS: We performed an 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay to evaluate the modifying effects of the chemicals on cell viability as the first screening. Then, induction of apoptosis was detected by means of a DNA fragmentation assay, a quantitative enzyme immunoassay, and morphological analysis using 4-diamidino-2-phenylindole staining. In addition, the modulating effects of the compounds on DNA synthesis of the cells with fixed doses of the compounds were analyzed by scoring the 5-bromo-2'-deoxyuridine labeling index. RESULTS: AUR, NOB, I3C, ACA, and ACE had apoptosis-inducing effects in a concentration- and time-dependent manner, some of which were followed by a reduction in replicating DNA synthesis. CGA, PA, SIN, GL, DIO, and HE had little modulating effect on cell viability, apoptosis, and DNA synthesis in this cell system. CONCLUSIONS: Our results suggest that AUR, I3C, ACA, NOB, and ACE might exert tumor-preventive action through apoptosis- and/or cell proliferation-dependent mechanisms and, on the other hand, CGA, PA, SIN, HE, DIO, and GL might be apoptosis- and cell proliferation-independent. These assays provided an initial tool for further mechanical studies of tumor-preventive agents and future applications to mechanism-based chemopreventive studies.

Modifying effects of dietary capsaicin and rotenone on 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis.

The effects of dietary administration of capsaicin and rotenone on 4-nitroquinoline 1-oxide (4-NQO)-induced tongue tumorigenesis were investigated in male F344 rats. In pilot studies, gavage with capsaicin and rotenone elevated the phase II enzymes glutathione S-transferase (GST) and quinone reductase (QR), in the liver and tongue. Also, a 10 week period of feeding of 500 p.p.m. capsaicin or rotenone together with 4-NQO exposure inhibited the occurrence of tongue dysplasia. Subsequently, a long-term study was conducted to test the protective effects of both compounds on 4-NQO-induced tongue carcinogenesis. One group was treated with 4-NQO alone (20 p.p.m. in drinking water for 8 weeks) and four other groups received the carcinogen treatment plus diets containing 500 p.p.m. test compounds for 10 weeks (initiation phase) or for 28 weeks (post-initiation phase). At the termination of the study (38 weeks), feeding of rotenone during the initiation phase, but not during the post-initiation phase, was found to significantly reduce the incidence of tongue squamous cell carcinoma (53% vs. 16%, 70% reduction, P b=e 0.0250) and severe dysplasia (80% vs. 42%, 70% reduction, P = 0.028). Capsaicin feeding during either the initiation or promotion phase and rotenone feeding during the promotion phase also reduced the frequency of tongue carcinoma without statistical significance. The treatment with two compounds especially rotenone lowered cell proliferation activity in the tongue, elevated phase II enzymes' activities of the liver and tongue, and increased the apoptotic index of tongue carcinoma. Although our results suggest that rotenone feeding during the initiation stage prevented 4-NQO-induced tongue carcinoma, chronic intravenous exposure of rotenone reproduces several features of human Parkinson's disease in rats (Nat. Neurosci., 3, 1301-1306, 2000), suggesting that additional studies to confirm the safety of rotenone are warranted.

Preventive effect of fermented brown rice and rice bran against colon carcinogenesis in male F344 rats.

Epidemiological and preclinical studies demonstrate that nutrition plays an important role in the etiology of cancer. It has been reported that rice components, especially rice germ plays a key role in prevention of cancer. The experiments described here examined the potential anticancer properties of brown rice fermented by Aspergillus Oryzae (FBRA) in male F344 rats using inhibition of the formation of azoxymethene (AOM) induced aberrant crypt foci (ACF) and tumors in the colon as the measure of preventive efficacy. The agent was administered at 2.5 and 5% levels in the diet during the initiation phase (during and until 1 week after carcinogen treatment) and/or post-initiation phase (beginning 1 week after carcinogen treatment) of carcinogenesis. In the ACF and tumor studies, rats were sacrificed 5 or 40 weeks after the initiation of AOM treatment (15 mg/kg body weight, once weekly for 3 weeks), respectively. Colonic ACF and tumors were evaluated histopathologically. Administration of 2.5 and 5% FBRA in the diet continuously during initiation and post-initiation period significantly inhibited the ACF formation in rats treated with AOM, compared with rats treated with AOM alone (99+/-24.1 and 79+/-18.4 vs. 139.5+/-27.7, respectively). In addition, administration of 5% FBRA in the diet during the post-initiation phase significantly suppressed the incidence (44 vs.18%) and multiplicity (0.93+/-0.96 vs. 0.18+/-0.40) of colon adenocarcinomas as compared to those given the control diet. In addition, 5% FBRA in the diet during post-initiation phase caused significant inhibition of cell proliferation in the colonic mucosa as compared to the group fed the control diet (81% reduction, p<0.05). These observations demonstrated for the first time that FBRA inhibits colon tumor development in rats, and suggest that it is a promising dietary supplement for prevention of human colon cancer.